Significant associations have been found between specific human leukocyte antigen (HLA) alleles and organ transplant rejection, autoimmune disease development, and the response to infection. Traditional searches for disease associations have conventionally measured risk associated with the presence of individual HLA alleles. However, given the high level of HLA polymorphism, the pattern of amino acid variability, and the fact that most of the HLA variation occurs at functionally important sites, it may be that a combination of variable amino acid sites shared (...) by several alleles (shared epitopes) are better descriptors of the actual causative genetic variants. Here we describe a novel approach to genetic association analysis in which genes/proteins are broken down into smaller sequence features and then variant types defined for each feature, allowing for independent analysis of disease association with each sequence feature variant type. We have used this approach to analyze a cohort of systemic sclerosis patients and show that a sequence feature composed of specific amino acid residues in peptide binding pockets 4 and 7 of HLA-DRB1 explains much of the molecular determinant of risk for systemic sclerosis. (shrink)

BackgroundThe ARRIVE (Animal Research: Reporting of In Vivo Experiments) guidelines are widely endorsed but compliance is limited. We sought to determine whether journal-requested completion of an ARRIVE checklist improves full compliance with the guidelines.MethodsIn a randomised controlled trial, manuscripts reporting in vivo animal research submitted to PLOS ONE (March–June 2015) were randomly allocated to either requested completion of an ARRIVE checklist or current standard practice. Authors, academic editors, and peer reviewers were blinded to group allocation. Trained reviewers performed outcome adjudication (...) in duplicate by assessing manuscripts against an operationalised version of the ARRIVE guidelines that consists 108 items. Our primary outcome was the between-group differences in the proportion of manuscripts meeting all ARRIVE guideline checklist subitems.ResultsWe randomised 1689 manuscripts (control: n = 844, intervention: n = 845), of which 1269 were sent for peer review and 762 (control: n = 340; intervention: n = 332) accepted for publication. No manuscript in either group achieved full compliance with the ARRIVE checklist. Details of animal husbandry (ARRIVE subitem 9b) was the only subitem to show improvements in reporting, with the proportion of compliant manuscripts rising from 52.1 to 74.1% (X2 = 34.0, df = 1, p = 2.1 × 10−7) in the control and intervention groups, respectively.ConclusionsThese results suggest that altering the editorial process to include requests for a completed ARRIVE checklist is not enough to improve compliance with the ARRIVE guidelines. Other approaches, such as more stringent editorial policies or a targeted approach on key quality items, may promote improvements in reporting. (shrink)

Saeculum: Gedenkschrift für Heinrich Otten anlässlich seines 100. Geburtstags. Edited by Andreas Müller-Karpe; Elisabeth Rieken; and Walter Sommerfeld. Studien zu den Boǧazköy-Texten, vol. 58. Wiesbaden: Harrassowitz Verlag, 2015. Pp. xi + 316, illus. €84.

Розкрито сутність поняття «рейтинг». Доведено значущість рейтингової оцінки для суб’єктів фінансового ринку, зокрема для страхових компаній, потенційних страхувальників, інвесторів та кредиторів.

"Williams's masterful translation satisfies (at last!) a long-standing need. There are lots of good translations of Augustine's great work, but until now we have been forced to choose between those that strive to replicate in English something of the majesty and beauty of Augustine's Latin style and those that opt instead to convey the careful precision of his philosophical terminology and argumentation. Finally, Williams has succeeded in capturing both sides of Augustine's mind in a richly evocative, impeccably reliable, elegantly readable (...) presentation of one of the most impressive achievements in Western thought--Augustine's Confessions." --Scott MacDonald, Professor of Philosophy and Norma K. Regan Professor in Christian Studies, Cornell University. (shrink)

_Education and Immigration_ comprises six reports that emerged from an EU funded comparative research project into the challenges posed to national education systems by immigration and its associated issues and problems. The immigration-related education policies and initiatives of six countries are explained, examined and compared. The book clearly delineates the historical, legal and sociological contexts of the various strategies, and how far these have been adhered to.

This book offers a critical introduction to the work of American philosopher D. G. Leahy (1937-2014). Leahy's fundamental thinking can be characterized as an absolute creativity in which all creating is 'live' -- a happening occurring now that manifests a supersaturated polyontological actuality that is essentially created by the logic that characterizes it. Leahy leaves behind the categorial presuppositions of modern thought, eclipsing both Cartesian and Hegelian subjectivities and introducing instead an essentially new form of thinking founded in a nondual (...) logic of creation. The new thinking delineates the absolute unicity of existence as a creative interactivity beyond all traditional dichotomies (such as one vs. many, unity vs. plurality, identity vs. change): a fully "digitized" actuality that is nothing but newness, which inherently implies nothing but change. Through this new form of thinking, change itself is revealed to be the very essence of reality and mind. Any reader looking for a quantum leap beyond the thrall of modern and postmodern fixations is invited to hear and apprehend this new thinking that refuses to be conditioned by paradigms, categories, species, genera, walls, bridges, boundaries, or abstractions: an essentially free thinking that embodies creative novelty itself. (shrink)

Responsibility for Human Rights provides an original theoretical analysis of which global actors are responsible for human rights, and why. It does this through an evaluation of the different reasons according to which such responsibilities might be assigned: legalism, universalism, capacity and publicness. The book marshals various arguments that speak in favour of and against assigning 'responsibility for human rights' to any state or non-state actor. At the same time, it remains grounded in an incisive interpretation of the world we (...) actually live in today, including: the relationship between sovereignty and human rights, recent events in 'business and human rights' practice, and key empirical examples of human rights violations by companies. David Karp argues that relevantly public actors have specific human rights responsibility. However, states can be less public, and non-state actors can be more public, than might seem apparent at first glance. (shrink)